Objective To establish a HPLC method for the determination of berberine hydrochloride in Zhixie Baotong granule. Methods The HPLC system consisted of the Ecosil C18（4. 6mm×250mm， 5μm） column， the mobile phase consisted of acetonitrile-0.05 mol/L KH2PO4（50 ∶ 50）， the flow rate was 1.0 mL/min， the UV detector was set at 350nm. Results The linear response range was 0.038～1.910 μg（r=0.9999）. The average recovery of puerarin was 98.25%， and RSD=1.61%. Conclusion The method is simple， rapid， accurate and repeatable. It can be applied in determination of berberine hydrochloride in Zhixie Baotong granule.